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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fat tissue is a significant source of endogenous tumor necrosis factor alpha (TNFalpha), the pluripotent cytokine that plays an important role as a mediator of the peripheral insulin resistance found in obesity. The majority of evidence for this role of TNFalpha is from studies in animal models of obesity. To explore further the role of TNFalpha in the pathogenesis of obesity-related insulin resistance in humans, we compared plasma levels of TNFalpha and the other main endocrine cytokine, interleukin-6 ([IL-6] both measured by enzyme-linked immunosorbent assay), in 26 obese women (body mass index [BMI] > 30 kg/m2) and 13 female controls (BMI < 26 kg/m2) without a history of recent or active infection. Glucose and insulin levels were measured at 0, 1, and 2 hours after a 75-g oral glucose load. There was no significant difference in plasma TNFalpha or IL-6 levels between obese and non-obese subjects overall (2.10 +/- 0.19 v 1.65 +/- 0.18 pg/mL and 2.06 +/- 0.29 v 1.50 +/- 0.17 pg/mL, respectively). However, TNFalpha levels were significantly elevated in obese subjects with a 2-hour glucose level more than 140 mg/dL (n = 8) compared with the other obese subjects (n = 18) and the non-obese controls (2.88 +/- 0.46 v 1.75 +/- 0.10 and 1.65 +/- 0.18 pg/mL, respectively, P < .01). Furthermore, the TNFalpha level correlated significantly with the waist to hip ratio ([WHR] r = .53, P < .01) and fasting and post-oral glucose tolerance test (OGTT) insulin levels (r = .47, P < .02), but not with the BMI, and was higher in obese women with a WHR more than 0.90 (n = 14) in comparison to those with a WHR less than 0.90 (n = 12, 2.47 +/- 0.29 v 1.66 +/- 0.18 pg/mL, respectively, P < .03). The corresponding plasma leptin level was significantly higher in obese women versus the control group (41.6 +/- 2.5 v22.3 +/- 2.9 ng/mL, P < .001) and was related to the BMI (r = .60, P < .01) but not to TNFalpha or the WHR. There were no significant differences in the corresponding IL-6 concentration between groups, and IL-6 did not correlate with TNFalpha, leptin, BMI, WHR, or insulin levels. In conclusion, circulating TNFalpha levels are higher in abdominal obesity compared with peripheral obesity, and may contribute to the insulin resistance that more commonly complicates the former pattern of fat distribution.
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PMID:Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity. 1053

The mechanism of insulin resistance in obesity is not fully understood. In muscle cells, the number of insulin receptor, the function of glucose transporter 4 and the activity of tyrosine kinase decrease. The rink of body fat accumulation and insulin resistance in muscle is thought through free fatty acid and tumor necrosis factor alpha secreted in adipose tissue. Thiazolidinediones (TZDs) are useful to reduce insulin resistance especially in obesity. TZDs seem to cause small weight gain, but to reduce visceral fat in 12-24 weeks. In longer period, it hasn't been studied very much. There are some unsolved problems. So now, targets of TZDs are obese diabetes failed in other medicines. When using TZDs, be cautious of excess eating and physical inactivity.
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PMID:[Obesity, insulin resistance and the implication of thiazolidinediones]. 1070 67

Recently, two G-->A polymorphisms at positions -308 and -238, in the promoter of the tumor necrosis factor alpha (TNF-alpha) gene, have been identified. These variants have, in different ethnic groups, been linked to estimates of insulin resistance and obesity. The objective of the present study was to investigate whether these genetic variants of TNF-alpha were associated with features of the insulin resistance syndrome or alterations in birth weight in two Danish study populations comprising 380 unrelated young healthy subjects and 249 glucose-tolerant relatives of type 2 diabetic patients, respectively. All study participants underwent an iv glucose tolerance test with the addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the polymorphisms by applying PCR restriction fragment length polymorphism. Neither of the variants was related to altered insulin sensitivity index or other features of the insulin resistance syndrome (body mass index, waist to hip ratio, fat mass, fasting serum lipids or fasting serum insulin or C-peptide). Birth weight and the ponderal index were also not associated with the polymorphisms. In conclusion, although the study was carried out on sufficiently large study samples, the study does not support a major role of the -308 or -238 substitutions of the TNF-alpha gene in the pathogenesis of insulin resistance or altered birth weight among Danish Caucasian subjects.
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PMID:The -238 and -308 G-->A polymorphisms of the tumor necrosis factor alpha gene promoter are not associated with features of the insulin resistance syndrome or altered birth weight in Danish Caucasians. 1077 Feb 22

Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are characteristic of the obese state and may contribute to the association between obesity and cardiovascular disease. In this study, we measured the rate of secretion of PAI-1 antigen in isolated subcutaneous and omental abdominal adipocytes from severely obese and non-obese individuals and studied the effect of selected cytokines on PAI-1 release using a suspension culture technique. PAI-1 secretion was approximately 2-fold greater in isolated fat cells from the obese versus non-obese subjects. In addition, PAI-1 mRNA levels were higher in adipose tissue samples from obese versus non-obese individuals (P < .05). PAI-1 release was also approximately 2-fold greater in omental versus subcutaneous adipocytes from both obese and non-obese subjects (each P < .05). A 24-hour exposure to 1 nmol/L tumor necrosis factor alpha (TNF-alpha) slightly increased PAI-1 release from both subcutaneous and omental adipocytes (30% +/- 21% and 17% +/- 18%, respectively, nonsignificant [NS]). Transforming growth factor beta 1 (TGF-beta1) induced a significant dose-dependent increase of PAI-1 release into the medium. Exposure to 400 pmol/L TGF-beta1 of subcutaneous and omental fat cells from both obese and non-obese individuals elevated PAI-1 secretion by 2-fold. These data provide evidence that human fat cells release a substantial amount of PAI-1 in a depot-specific manner and that TGF-beta1 particularly contributes to the regulation of PAI-1 secretion.
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PMID:Effect of tumor necrosis factor alpha and transforming growth factor beta 1 on plasminogen activator inhibitor-1 secretion from subcutaneous and omental human fat cells in suspension culture. 1083 Nov 81

In this chapter, we summarize our studies on plasminogen activator inhibitor 1 (PAI-1), tissue factor, and transforming growth factor beta (TGF-beta) expression in obesity, using genetically obese mice as a model. These studies emphasize the key role played by the adipocyte, a cell whose numbers, size, and metabolic activity are grossly altered in obesity/NIDDM. They also implicate multiple cytokines, hormones, and growth factors in the abnormal expression of these and perhaps other hemostatic genes by adipocytes in obesity/NIDDM. These studies demonstrate that tumor necrosis factor alpha (TNF-alpha) plays a central role in the expression of hemostatic genes in this disorder.
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PMID:The fat mouse. A powerful genetic model to study hemostatic gene expression in obesity/NIDDM. 1086 47

Severe quantitative and qualitative brown adipocyte defects are common in obesity. To investigate whether aberrant expression of tumor necrosis factor alpha (TNF-alpha) in obesity is involved in functional brown fat atrophy, we have studied genetically obese (ob/ob) mice with targeted null mutations in the genes encoding the two TNF receptors. The absence of both TNF receptors or p55 receptor alone resulted in a significant reduction in brown adipocyte apoptosis and an increase in beta(3)-adrenoreceptor and uncoupling protein-1 expression in obese mice. Increased numbers of multilocular functionally active brown adipocytes, and improved thermoregulation was also observed in obese animals lacking TNF-alpha function. These results indicate that TNF-alpha plays an important role in multiple aspects of brown adipose tissue biology and mediates the abnormalities that occur at this site in obesity.
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PMID:Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity. 1088 31

The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance. To that end, we compared: 1) serum concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), and leptin in eight healthy lean control females and in android obese female without (n = 14) and with (n = 7) type 2 diabetes; and 2) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet (VLCD). As compared with lean controls, obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin, IL-6, TNFalpha, and C-reactive protein. In the whole group, IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values. VLCD resulted in weight loss and decreased body fat mass (approximately 3 kg). Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels. In contrast, VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum. These results suggest that, as for leptin, circulating IL-6 concentrations reflect, at least in part, adipose tissue production. The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients.
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PMID:Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. 1099 30

Over-eating and physical inactivity in combination with genetic factors play the most important roles in the development of over weight in humans. The common genetic components behind excess accumulation of body fat are so far unknown. Studies of candidate genes indicate that most of the genes that associate with obesity control important functions of adipose tissue as well. Furthermore, structural variations in these genes may alter adipose tissue function in a way that promotes obesity. The genes which both are functional in human adipose tissue and associate with obesity are: hormone sensitive lipase, beta2 and beta3-adrenoceptors, tumor necrosis factor alpha, low density lipoprotein receptor, uncoupling protein-1 and peroxisome proliferator activated receptor gamma-2. Other genes are mostly important for obesity among women (for example beta2 -and beta3-adrenoceptors, low density lipoprotein receptor and tumor necrosis factor alpha). Some of these genes may promote obesity by gene-gene interactions (for example beta3-adrenoceptors and uncoupling protein-1) or gene-environmental interactions (for example beta2-adrenoceptors and physical activity). Few genes with no known function in adipose tissue have shown a firm association with excess body fat. The latter suggests that the important human obesity genes also control adipose tissue function. Therefore it might be of value to focus the further hunt for obesity genes on the fat tissue.
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PMID:Hunting for human obesity genes? Look in the adipose tissue! 1112 44

In obese subjects, the levels of tumor necrosis factor alpha (TNF-alpha) expression and protein synthesis in adipocytes are increased. A recent study of Caucasians suggested that the TNF-alpha gene promoter region polymorphism at position -308 influences insulin resistance and percent body fat and increases serum leptin levels, although conflicting data are also reported. The present study was performed to investigate the relationship between this polymorphism and the body mass index (BMI), blood pressure, glucose and lipid profiles, and serum leptin in 122 healthy young men aged 21 to 29, 177 older men aged 45 to 65, and 71 type 2 diabetic male patients aged 42 to 78. The BMI, blood pressure, and fasting plasma glucose (FPG), serum lipids, uric acid, insulin, and leptin concentrations were measured. The TNF-alpha G-308A polymorphism was assessed by the polymerase chain reaction restriction fragment length polymorphism method. In the young group, 4 subjects (3.3%) were heterozygous for the TNF2 (G-308A-positive) allele, but there were no significant differences between the TNF1 (wild-type) and TNF2 groups in any measured anthropometric or metabolic parameter. In the older group, the frequency of the TNF2 group was 2.8%, and FPG was significantly higher in the TNF2 versus the TNF1 group (108 +/- 7 v 99 +/- 9 mg/dL, P= .042 by Mann-Whitney Utest). Plasma triglycerides and the insulin resistance index tended to be higher and high-density lipoprotein (HDL) cholesterol tended to be lower in the TNF2 group (P = .06, .20, and .07, respectively), although these differences were not statistically significant. In type 2 diabetic subjects, the frequency of the TNF2 group was also 2.8%, and there were no significant differences between the TNF1 and TNF2 groups in any parameter. HDL cholesterol tended to be lower (P = .10) in the TNF2 group, although it was not statistically significant. In conclusion, no major difference was associated with TNF1 and TNF2 polymorphisms in terms of obesity, blood pressure, lipids, or glucose in young, older, or diabetic Japanese men, although FPG was significantly higher in older men, possibly through increased insulin resistance.
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PMID:Tumor necrosis factor alpha gene G-308A polymorphism, insulin resistance, and fasting plasma glucose in young, older, and diabetic Japanese men. 1114 26

A variety of cytokines and other compounds are produced in the human adipose tissue and may have autocrine functions in the adipose tissue as well as be involved in the complications seen in association with obesity. Because it recently has been reported that interleukin 8 (IL-8), through its effects on the macrophage and endothelial cell, may be involved in the pathogenesis of atherosclerosis, we found it of interest to investigate whether IL-8 is produced in human adipose tissue in vitro. Human sc adipose tissue was investigated both in incubations with whole adipose tissue fragments as well as with isolated mature adipocytes. In adipose tissue fragments, IL-1beta (3 nM) and tumor necrosis factor alpha (0.6 nM) were able to stimulate IL-8 production by 12-fold and 5-fold, respectively (P < 0.001), when incubated for 48 h. Incubations with isolated adipocytes were performed up to 6 h, and IL-1beta and tumor necrosis factor alpha significantly increased IL-8 production by 50-60% (P < 0.05). Dexamethasone (50 nM) decreased IL-8 production from adipose tissue fragments by 57% (P < 0.01) and from adipocytes by 37% (P < 0.05). IL-8 messenger RNA expression in adipocytes incubated with IL-1beta was increased already after 2 h (P < 0.05). Thus, the effect of proinflammatory cytokines and dexamethasone on IL-8 production in adipose tissue seems to be mediated at the transcriptional level. In conclusion, it is demonstrated for the first time that IL-8 is produced and released from human adipose tissue and from isolated adipocytes in vitro, which may indicate that IL-8 from adipose tissue could be involved in some of the obesity-related complications.
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PMID:Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. 1123 19


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